Analysis of a large single institution cohort of related donors fails to detect a relation between SDF1/CXCR4 or VCAM/VLA4 genetic polymorphisms and the level of hematopoietic progenitor cell mobilization in response to G-CSF.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2020
Historique:
received: 09 07 2019
accepted: 24 01 2020
entrez: 6 3 2020
pubmed: 7 3 2020
medline: 13 6 2020
Statut: epublish

Résumé

We studied a cohort of 367 healthy related donors who volunteered to donate their hematopoietic stem cells for allogeneic transplantation. All donors were homogeneously cared for at a single institution, and received rhG-CSF as a mobilization treatment prior to undergoing apheresis. Peripheral blood CD34+ cell counts were used as the main surrogate marker for rhG-CSF induced mobilization. We searched whether inter-individual variations in known genetic polymorphisms located in genes whose products are functionally important for mobilization, could affect the extent of CD34+ mobilization, either individually or in combination. We found little or no influence of individual SNPs or haplotypes for the SDF1, CXCR4, VCAM and VLA4 genes, whether using CD34+ cell counts as a continuous or a categorical variable. Simple clinical characteristics describing donors such as body mass index, age and possibly sex are more potent predictors of stem cell mobilization. The size of our cohort remains relatively small for genetic analyses, however compares favorably with cohorts analyzed in previously published reports suggesting associations of genetic traits to response to rhG-CSF; notwithstanding this limitation, our data do not support the use of genetic analyses when the choice exists of several potential donors for a given patient.

Identifiants

pubmed: 32134938
doi: 10.1371/journal.pone.0228878
pii: PONE-D-19-19237
pmc: PMC7058310
doi:

Substances chimiques

CXCL12 protein, human 0
CXCR4 protein, human 0
Chemokine CXCL12 0
Integrin alpha4beta1 0
Receptors, CXCR4 0
Vascular Cell Adhesion Molecule-1 0
Granulocyte Colony-Stimulating Factor 143011-72-7

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0228878

Déclaration de conflit d'intérêts

Both Dr Sylvain Garciaz and myself Christian Chabannon received funding from SANOFI S.A. as speakers during industry-sponsored symposium. I also benefited of an invitation – including financial support for traveling – to a scientific meeting as a delegate. In addition, SANOFI S.A. funded another and different clinical project on autologous stem cell mobilization and collection that was conducted at Institut Paoli-Calmettes, the Comprehensive Cancer Center in Marseille, France. This does not alter our adherence to PLOS ONE policies on sharing data and materials (as detailed online in the journal guide for authors http://journals.plos.org/plosone/s/competinginterests).

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Auteurs

Sylvain Garciaz (S)

Institut Paoli-Calmettes, Comprehensive Cancer Center, Marseille, France.
Aix-Marseille Univ, Inserm, CNRS, Institut Paoli-Calmettes, CRCM, Marseille, France.

Patrick Sfumato (P)

Institut Paoli-Calmettes, Comprehensive Cancer Center, Marseille, France.

Angela Granata (A)

Institut Paoli-Calmettes, Comprehensive Cancer Center, Marseille, France.

Anne-Marie Imbert (AM)

Institut Paoli-Calmettes, Comprehensive Cancer Center, Marseille, France.

Claire Fournel (C)

Institut Paoli-Calmettes, Comprehensive Cancer Center, Marseille, France.

Boris Calmels (B)

Institut Paoli-Calmettes, Comprehensive Cancer Center, Marseille, France.
Aix-Marseille Univ, Inserm, CNRS, Institut Paoli-Calmettes, CRCM, Marseille, France.
Centre d'Investigations Cliniques de Marseille, module Biothérapies, Inserm CBT, Marseille, France.

Claude Lemarie (C)

Institut Paoli-Calmettes, Comprehensive Cancer Center, Marseille, France.
Aix-Marseille Univ, Inserm, CNRS, Institut Paoli-Calmettes, CRCM, Marseille, France.
Centre d'Investigations Cliniques de Marseille, module Biothérapies, Inserm CBT, Marseille, France.

Jacques Chiaroni (J)

Etablissement Français du Sang PACA Corse, Biologie des Groupes Sanguins, Marseille, France.
Aix Marseille Univ, CNRS, EFS, ADES, Marseille, France.

Didier Blaise (D)

Institut Paoli-Calmettes, Comprehensive Cancer Center, Marseille, France.
Aix-Marseille Univ, Inserm, CNRS, Institut Paoli-Calmettes, CRCM, Marseille, France.

Jean-Marie Boher (JM)

Institut Paoli-Calmettes, Comprehensive Cancer Center, Marseille, France.

Christophe Picard (C)

Etablissement Français du Sang PACA Corse, Biologie des Groupes Sanguins, Marseille, France.
Aix Marseille Univ, CNRS, EFS, ADES, Marseille, France.

Christian Chabannon (C)

Institut Paoli-Calmettes, Comprehensive Cancer Center, Marseille, France.
Aix-Marseille Univ, Inserm, CNRS, Institut Paoli-Calmettes, CRCM, Marseille, France.
Centre d'Investigations Cliniques de Marseille, module Biothérapies, Inserm CBT, Marseille, France.

Julie di Cristofaro (J)

Etablissement Français du Sang PACA Corse, Biologie des Groupes Sanguins, Marseille, France.
Aix Marseille Univ, CNRS, EFS, ADES, Marseille, France.

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Classifications MeSH